OBJECTIVE: To establish when the formation of antibodies against T-lymphocyte-dependent and -independent antigens is impaired during HIV infection. DESIGN: Prospective study on antibody formation before and 30 days and 60 days after vaccination with tetravalent influenza vaccine, tetanus toxoid and pneumococcal vaccine; booster with influenza vaccine was administered 30 days after initial vaccination. SETTING: Outpatient clinic of University Hospital Leiden. PARTICIPANTS: Fifty-one HIV-infected individuals and 10 healthy controls. RESULTS: In HIV-infected individuals with < 100 x 10(6)/l CD4+ lymphocytes almost no influenza antibodies were formed; CD4+ counts between 100 and 300 x 10(6)/l correlated with suboptimal antibody formation; CD4+ counts > or = 300 x 10(6)/l yielded more individuals with protective antibody titres. Thirty days after vaccination, protective antibody titres against the four influenza strains had been achieved in 24% of all HIV-infected individuals for A/Beijing (H3N2) (controls, 90%), 59% for A/Taiwan (H1N1) (controls, 80%), 18% for B/Beijing (controls, 30%) and 37% for B/Panama (controls 90%). Booster vaccination after 1 month did not increase antibody levels. Anti-tetanus toxin antibody formation, which is also T-lymphocyte-dependent, was correlated with the number of CD4+ lymphocytes. After pneumococcal vaccination (T-lymphocyte-independent), normal antibody formation was observed in HIV-infected individuals, including those with low CD4+ counts. CONCLUSIONS: Influenza vaccination should not be administered to HIV-infected individuals with CD4+ counts < 100 x 10(6)/l; pneumococcal vaccination can be offered to all HIV-infected individuals and a tetanus toxoid booster should be administered when indicated.